Drug Interaction Report

GENERALLY AVOID: Based on in vitro inhibition data, coadministration with dalfopristin-quinupristin may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme, including certain agents that can cause prolongation of the QTc interval (e.g., cisapride, disopyramide, pimozide, quinidine, tacrolimus). High plasma levels of these agents have been rarely associated with ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation, and torsade de pointes, as well as cardiac arrest and sudden death.

MANAGEMENT: Given the potential for serious and life-threatening adverse cardiac events associated with increased plasma levels of agents that may prolong the QTc interval, concomitant use with dalfopristin-quinupristin should be avoided if they are known to be substrates of CYP450 3A4.

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.